In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2

Chakraborty, Rajkumar; Bhattacharje, Gourab; Baral, Joydeep; Manna, Bharat; Mullick, Jayati; Mathapati, Basavaraj; Abraham, Priya; Madhumathi, J; Hasija, Yasha; Ghosh, Amit; Das, Amit Kumar

doi:10.1016/j.compbiomed.2022.105788

Cited by 14 publications

(4 citation statements)

References 106 publications

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“…Various recent studies have shown that the strategy of combining the in silico drug screening/discovery with in vitro validation of potential hits in a cell-based system has a significant advantage over classical drug discovery approaches and increases the chances of selecting the best antiviral hit compound for in vivo testing, as well as therapeutic profiling [37,48,[52][53][54][55][56][57]. The present study confirms the utility of preliminary in silico screening of library compounds for medicinal use.…”

Section: Discussionsupporting

confidence: 80%

In silico identification of chikungunya virus replication inhibitor validated using biochemical and cell‐based approaches

Chaudhary,

Kumar,

Bala Sharma

et al. 2024

The FEBS Journal

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Discovering an alternative therapy with a long‐lasting effect on symptoms caused by chikungunya virus (CHIKV) infection is prompted by the lack of a vaccine and the absence of safe, effective and non‐toxic medications. One potential strategy is synthesizing or identifying small compounds that can specifically target the active site of an essential enzyme and prevent virus replication. Previous site‐directed mutagenesis studies have demonstrated the crucial role of the macrodomain, which is a part of non‐structural protein 3 (nsP3), in virus replication. Exploiting this fact, the macrodomain can be targeted to discover a natural substance that can inhibit its function and thereby impede virus replication. With this aim, the present study focused on potential CHIKV nsP3 macrodomain (nsP3MD) inhibitors through in silico, in vitro and cell‐based methods. Through virtual screening of the natural compound library, nine nsP3MD inhibitors were initially identified. Molecular dynamics (MD) simulations were employed to evaluate these nine compounds based on the stability of their ligand–receptor complexes and energy parameters. Target analysis and ADMET (i.e. absorption, distribution, metabolism, excretion and toxicity) prediction of the selected compounds revealed their drug‐like characteristics. Subsequent in vitro investigation allowed us to narrow the selection down to one compound, N‐[2‐(5‐methoxy‐1H‐indol‐3‐yl) ethyl]‐2‐oxo‐1,2‐dihydroquinoline‐4‐carboxamide, which exhibited potent inhibition of CHIKV growth. This molecule effectively inhibited CHIKV replication in the stable embryonal rhabdomyosarcoma cell line capable of producing CHIKV. Our findings demonstrate that the selected compound possesses substantial anti‐CHIKV nsP3MD activity both in vitro and in vivo. This work provides a promising molecule for further preclinical studies to develop a potential drug against the CHIKV.

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Section: Discussionsupporting

confidence: 80%

In silico identification of chikungunya virus replication inhibitor validated using biochemical and cell‐based approaches

Chaudhary,

Kumar,

Bala Sharma

et al. 2024

The FEBS Journal

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show abstract

“… 28 , 29 Recently, indomethacin has been shown to have antiviral activity against a number of viruses, including herpesviruses, hepatitis B virus, vesicular stomatitis virus, and coronaviruses 30 , 31 , 32 , 33 Previous studies have demonstrated indomethacin as an inhibitor of SARS-CoV, canine coronavirus, and SARS-CoV-2. 32 , 34 This study further extended its antiviral activity against different variants of SARS-CoV-2 and three species of seasonal coronaviruses. In our SARS-CoV-2 infected human lung cell line, the EC50 value of indomethacin was determined as 16.369 μM by qRT-PCR quantification of viral genomes.…”

Section: Discussionmentioning

confidence: 78%

Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response

Li¹,

Xu²,

Vries³

et al. 2023

iScience

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“…As an effective and rapid method for drug discovery, a “drug repurposing” strategy was also applied to screen available approved drugs to combat COVID-19 ( Batalha et al., 2021 ; Xu et al., 2021 ). This found that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INM) can combat a series of coronaviruses including canine coronavirus, SARS-CoV-1, and SARS-CoV-2 ( Chakraborty et al., 2022 ; Marinella, 2020 ; Zeng et al., 2020 ), resulting in a phase II clinical trial for treatment of patients with mild COVID-19 symptoms (NCT04344457). Although the detailed mechanism of action of INM as a NSAID has not yet been understood, this has proven effective in many kinds of other syndromes because of the analgesic and antipyretic properties ( Rao et al., 2010 ).…”

Section: The Emergence Of Antiviral Protacsmentioning

confidence: 99%

Antiviral PROTACs: Opportunity borne with challenge

Liang¹,

Wu²,

Lan³

et al. 2023

Cell Insight

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In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2

Cited by 14 publications

References 106 publications

In silico identification of chikungunya virus replication inhibitor validated using biochemical and cell‐based approaches

In silico identification of chikungunya virus replication inhibitor validated using biochemical and cell‐based approaches

Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response

Antiviral PROTACs: Opportunity borne with challenge

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